Prophosphatrane deprotonation of solvents

ABSTRACT

A method is disclosed for deprotonating a compound comprising treating the compound with a base of the general formula: ##STR1## in the presence of a nitrile solvent; wherein R 1 , R 2  and R 3  are each individually H, (C 1  -C 15 )alkyl, (C 6  -C 9 )aryl, (C 1  -C 4 )alkyl(C 6  -C 9 )aryl, ((C 1  -C 4 )alkyl) 3  Si, or (C 6  -C 9 )aryl(C 1  -C 4 )alkyl.

This invention was made with support of the U.S. Department of Commerceunder Grant No. ITA 87-02. The U.S. Government has certain rights in theinvention.

BACKGROUND OF THE INVENTION

Strong non-ionic bases play an important role in organic synthesisbecause of the milder reaction conditions they generally permit, theenhanced reactivity of the more naked anions in the poorly associatedion pairs formed upon substrate deprotonation by such bases (in contrastto ionic bases), and the better solubility of non-ionic bases in organicsolvents at or below room temperature, as required by some reactions.See, for example, R. Schwesinger, Chimia, 39, 269 (1985); T. Pietzonkaet at., Chem. Ber., 124, 1837 (1991); and R. Schwesinger et at., Angew.Chem. Int. Ed. Eng., 26, 1167 (1987).

Reagents which are known to be useful for abstracting a proton from awide variety of organic, organometallic, or inorganic substrates arecommercially available. An ideal proton abstractor has the capability ofabstracting protons from molecules reluctant to release protons and ofholding the abstracted proton tightly. It is preferable, for ease ofprocessing in complex organic syntheses, that once the proton abstractorhas abstracted a proton, that it not induce unwanted side reactions andthat it be easily separable as a stable product from the remainingportion of the reactants.

Commercially available strong bases, such as 1,8-diazabicyclo5.4.0!undec-7-ene (DBU) and 1,5-diazabicyclo 4.3.0!non-5-ene (DBN)(Aldrich Chemical Company), the structures of which are shown below, areknown in the art and are useful as proton abstracting reagents. ##STR2##The synthesis of trans Vitamin A and its various isomers has beenaccomplished using bases such as DBN. See, for example, Oediger, H. etat., Chem. Ber., vol. 99, p. 2012 (1966).

The proazaphosphatrane P(MeNCH₂ CH₂)₃ N (1) is an even strongernon-ionic base (or "superbase") than the above examples and is alsouseful as a catalyst for the conversion of isocyanates to industriallyimportant isocyanurates. ##STR3## See, for example, J. Verkade et at.,(U.S. Pat. No. 5,260,436); J. Verkade, (U.S. Pat. No. 5,051,533); and H.Schmidt et at., Z. Anorg. Allg. Chem., 578, 75 (1990). Theprophosphatrane P(MeNCH2CH2)3N, however, is a large, bulky molecule. It,therefore, can fail to extract a proton from a molecule in which theproton to be abstracted is hindered by nearby substituents. Protonabstraction has been especially problematic for certain precursormolecules to Vitamin A, because they present steric hindrancedifficulties.

Thus, a need exists for a more efficient chemical process thatfacilitates proton abstraction from large substrate compounds which, dueto their molecular structures, sterically hinder access of "superbases"to protons.

SUMMARY OF THE INVENTION

The present invention provides a method for deprotonating a compoundcomprising treating the compound with a base of the formula: ##STR4## inthe presence of a nitrile solvent; wherein R¹, R² and R³ are eachindependently substituents that are nonreactive under conditions of thereaction. Preferably, R', R² and R³ are each individually H, (C₁-C₁₅)alkyl, (C₆ -C₉)aryl, (C₁ -C₄)alkyl(C₆ -C₉)aryl, ((C₁ -C₄)alkyl)₃Si, or (C₆ -C₉)aryl(C₁ -C₄)alkyl. More preferably, R¹, R² and R³ areeach individually H, (C₁ -C₄)alkyl, (C₆ -C₉)aryl, or (alk)₃ Si whereineach alk is (C₁ -C₄)alkyl. Of these, R¹, R² and R³ are preferably eachindividually hydrogen or (C₁ -C₈)alkyl (more preferably, hydrogen or (C₁-C₄)alkyl, and most preferably, hydrogen or methyl).

The compound to be deprotonated by the method of the present inventioncan be a bulky molecule such as a Vitamin A precursor. For example, thecompound can be (2Z,4E,8E)-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,8-nonatrien-1-ylacetate or(3E,5E,8E)-2-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohen-1-yl)-3,5,8-nonatrien-1-ylacetate.

The nitrile solvent of the present invention preferably is of theformula R⁴ R⁵ CHCN, wherein R⁴ and R⁵ are each individually hydrogen;saturated or unsaturated, substituted or unsubstituted linear (C₁-C₈)alkyl; or substituted or unsubstituted (C₆ -C₄)aryl. Morepreferably, R⁴ and R⁵ are each hydrogen. Most preferably, the nitrilesolvent is acetonitrile.

DETAILED DESCRIPTION OF THE INVENTION

It has been discovered that nitriles, such as acetonitrile (CH₃ CN),when used in conjunction with, for example, the superbase P(MeNCH₂ CH₂)₃N, produce a small, potent base (e.g., ⁻ CH₂ CN) which effectivelydeprotonates larger substrate molecules. It was previously observed thatthe proazaphosphatrane P(MeNCH₂ CH₂)₃ N was not efficient atdeprotonating the precursor bromide (3) to Vitamin A. ##STR5## Thecombination of this superbase with nitriles, such as acetonitrile,however, is surprisingly effective in deprotonating large, bulkymolecules such as compound 3. Further, the combination of a phosphatraneand a nitrile in accordance with this invention unexpectedly allows thedeprotonating reaction to take place at room temperature (i.e., 25°-30°C.).

The reaction of the present method is summarized in reaction Scheme Ibelow: ##STR6## wherein a group R is a substituent which is nonreactiveunder conditions of the reaction. Herein when it is said that a group R(for example R¹, R² and R³) is nonreactive under the reaction conditionsit is meant that the group R is such that it does not participate in thereaction and it does not undergo chemical change or transformationduring the reaction. The R groups should also be such that they do notprevent the reaction. Herein when it is said that an R group (forexample R¹, R² and R³) should be chosen such that it does not "prevent"reaction, it is meant that the group is selected such that the reactantscan react in the manner described. For example, the R groups are chosensuch that they do not provide sufficient steric hindrance fornonreactivity, nor do they prevent sufficient solubility for reaction.Herein guidance with respect to "nonreactive" R groups and R groups thatdo not "prevent" reaction is provided in each instance by representativegroups. It is not meant, however, that the lists are exclusive.

According to the method of the invention, a target compound to bedeprotonated is treated with a strong base in the presence of a nitrilesolvent. The strong base is preferably a non-ionic prophosphatrane baseaccording to the general formula (compound 2): ##STR7## also sometimesreferred to as "superbase." R¹, R² and R³ are preferably eachindividually H, (C₁ -C₁₅)alkyl, (C₆ -C₉)aryl, (C₁ -C₄)alkyl(C₆ -C₉)aryl,(C₁ -C₄)alkyl!₃ Si, or (C₆ -C₉)aryl(C₁ -C₄)alkyl. More preferably, R¹,R² and R³ are each individually H, (C₁ -C₉)alkyl, (C₆ -C₉)aryl, or(alk)₃ Si wherein each alk is (C₁ -C₄)alkyl. Of these, R¹, R² and R³ arepreferably each independently selected from the group consisting ofhydrogen and (C₁ -C₈)alkyl. It is even more preferred that R¹, R² and R³are selected from the group consisting of hydrogen and (C₁ -C₄)alkyl.Most preferably, R¹, R² and R³ are hydrogen or methyl. As used herein"individually" or "independently" mean that the R groups can be the sameor different. A particularly preferred base, according to the method ofthe invention, is trimethyltriazaprophosphatrane, P(MeNCH₂ CH₂)₃ N (1).##STR8##

Synthesis of preferred bases according to the present invention isgenerally described in U.S. Pat. No. 5,051,533, the disclosure of whichis incorporated herein by reference. Briefly, as shown in Scheme IIbelow, the synthesis of 1 can be accomplished using C1P(NMe₂)₂ andtris-(betamethylaminoethyl)amine (trimethyl-TREN). ##STR9##

The prophosphatrane can be prepared as the hydrochloride by adding asolution of (HMeNCH₂ CH₂)₃ N in CH₂ Cl₂ over a period of five minutes toa stirred solution of C1P(NMe₂)₂ in CH₂ Cl₂. Stirring is continued atroom temperature for one hour followed by removal of the solvent toafford the phosphatranyl chloride. The salt is recrystallized fromhexane/chloroform at -20° C. The product is converted to thecorresponding prophosphatrane by adding the salt dissolved inacetonitrile to a suspension of potassium tertiary butoxide inacetonitrile. The solvent is removed under vacuum and the residueextracted with hexanes. The residue is purified by vacuum sublimation togive the prophosphatrane.

An improved and preferred synthesis of base 1 is described in Verkade etal., Tetrahedron Lett., 34, 2903 (1993). Briefly, (HMeNCH₂ CH₂)₃ N isadded to a stirred solution of C1P(NEt₂)₂ in dry CH₃ CN. After stirring,the reaction mixture is transferred to a flask containing t-BuOK in dryCH₃ CN. After stirring, the reaction mixture, the solvent is removedunder vacuum and the residue is extracted with dry pentane. The extractis evaporated using a vacuum to give a white solid which is purified byvacuum sublimation giving spectroscopically pure proazaphosphatrane.

Nitrile solvents which can be used in accordance with the invention areof the general formula R⁴ R⁵ CHCN, where R⁴ and R⁵ are eachindependently selected from the group consisting of hydrogen; saturatedor unsaturated, substituted or unsubstituted linear (C₁ -C₈)alkyl; orsubstituted or unsubstituted (C₆ -C₁₄)aryl. Most preferably R⁴ and R⁵are each hydrogen (i.e., acetonitrile).

As illustrated in the Examples, target compounds can be deprotonated byreacting the compound with a superbase P(RNCH₂ CH₂)₃ N in a nitrilesolvent HCR₂ CN with no criticality of temperature. Advantageously, thereaction can take place at room temperature, i.e., about 25°-30° C.

Reasonable modifications and variations are possible from the foregoingdisclosure without departing from either the spirit or scope of thepresent invention as defined by the claims. Objects and advantages ofthis invention will now be illustrated by the following examples, butthe particular materials and amounts thereof recited in these examples,as well as other conditions and details, should not be construed tounduly limit this invention.

EXPERIMENTAL EXAMPLES

Unless otherwise noted, materials were obtained from commercialsuppliers and were used without purification. Solvents were reagentgrade, pre-dried over molecular sieves, and when necessary, distilledfrom sodium-benzophenone ketyl prior to use (THF, ether). Removal ofsolvents from oily reaction products, was carried out by applying vacuumand magnetically stirring at room temperature until 20 mTorr wasachieved. However, residual hexane was still present especially forviscous compounds as judged from their ¹ H NMR spectra. Efforts toremove hexane by heating under vacuum resulted in decomposition.

¹ H NMR spectra were measured on Nicolet NT-300 and Varian VXR-300 NMRspectrometers in chloroformed while ¹³ C and ³¹ p NMR spectra wererecorded on a Varian VXR-300 NMR spectrometer in chloroformed andacetonitrile-d₃, respectively. Chemical shifts are reported in ppmdownfield from tetramethylsilane using chloroform (¹ H, 7.23 ppm) andchloroform-d (¹³ C, 77.07 ppm) resonances as secondary standards. ¹ Hand ¹³ C chemical shift assignments were supported by 2D ¹ H-¹ Hcorrelations performed on 3 and 5 as a mixture, and mixtures of 6a and6b, and by 2D ¹ H-¹³ C correlations recorded for 6a and 6b as a mixture(structures of these compounds are shown below). 2D spectra wereobtained on a Varian VXR-300 spectrometer using standard COSY and HETCORexperiments.

For preparative chromatographic separations, silica gel (60-200 mesh, EMScience) was used, except for Vitamin A isomers, for which onlydeactivated alumina (neutral, Baker) was found useful. TLC analyses wereperformed using plates precoated with silica gel (IB-2 and IB-F) oralumina (IB-F) (both Baker-flex from Baker). The following solventsystems were employed: hexane-ethyl acetate, 3:1, v/v (for silica gelplates); and hexane-ethyl acetate, 10:1, v/v (for alumina plates).Trimethylsulfonium methylsulfate was prepared in 88% yield by thereaction of dimethylsulfate with dimethyl sulfide in acetone. P. Mossetet al., Synthesis Communications, 15, 749 (1985).

EXAMPLE 1 Reaction of Phosphorous Tribromide with 4 to PrepareProtonated Intermediate Compound

To a solution of 10 mmol (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraene-1-ol (4) in ether (10 ml), PBr3(12 mmol) was injected at -20° C. under argon. ##STR10## The reactionmixture was stirred for one hour which allowed it to reach roomtemperature. The mixture was then diluted with ether (40 ml) andsequentially washed with cold brine, aqueous NaHCO₃, and brine untilneutral. Finally, the resulting product was dried over MgSO₄. Afterevaporation of ether, the crude product was left in vacuo (0.02 Tort) togive a mixture of the Vitamin A precursors (2Z, 4E,8E)-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,8-nonatrien-1-ylacetate (two isomers 3a and 3b) and(3E,5E,8E)-2-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohen-1-yl)-3,5,8-nonatrien-1-ylacetate (5) as a yellow oil in 85-95% yield. Since this material slowlyrams brown when left at room temperature, it was immediately used in thenext step. ##STR11## The following data were obtained from NMRspectroscopy of the resulting product:

3a: ¹ H NMR: δ 0.95 and 0.96 (25, H₃ C16,17), 1.16 (d, H3C19, J=6.8 Hz),1.35-1.45 (m, H₂ C2), 1.50-1.60 (m, H₂ C3), 1.64 (bs, H₃ C18), 1.84 (d,H₃ C20, J=0.9 Hz), 1.93 (bt, H₂ C4, J=6 Hz), 2.03 (s, CH₃ CO), 2.55(bsx, HC9, J=7 Hz), 4.59 (dd, HC10, J=10.2 Hz, J=5.0 Hz), 4.67 (d, H₂C15, J=7.3 Hz), 5.28 (dd, HCS, J=15.7 Hz, J=8.3 Hz), 5.51 (bt, HC14, J=7Hz), 5.88 (bd, HC7, J=15.9 Hz), 5.96 (dd, HC11, J=15.4 Hz, J=10.2 Hz),6.54 (d, HC12, J=15.3 Hz).

3b: ¹ H NMR: δ 0.92 and 0.93 (25, H3C16,17), 1.18 (d, H₃ C19, J=6.8 Hz),1.35-1.45 (m, H₂ C2), 1.50-1.60 (m, H₂ C3), 1.59 (d, H₃ C18, J=0.8),1.83 (d, H₃ C20, J=1.8 Hz), 1.92 (bt, H₂ C4, J=6 Hz), 2.03 (s, CH₃ CO),2.65 (bsx, HC9, J=7 Hz), 4.53 (dd, HC10, J=10.2 Hz, J=6.7 Hz), 4.66 (d,H₂ C15, J=7.2 Hz), 5.23 (dd, HC8, J=15.7 Hz, J=8.3 Hz), 5.49 (bt, HC14,J=7.2 Hz), 5.88 (bd, HC7, J=15.9 Hz), 5.91 (dd, HCl 1, J=15.3 Hz, J=10.2Hz), 6.52 (d, HC12, J=15.3 Hz).

5: ¹ H NMR: δ 0.95 (s, H₃ C16,17), 1.13 (d, H₃ C19, J=7.0 Hz), 1.35-1.45(m, H₂ C2), 1.50-1.60 (m, H₂ C3), 1.64 (bs, H₃ C18), 1.80 (bs, H₃ C20),1.92 (bt, H₂ C4), 2.01 (s, CH₃ CO), 2.97 (bsx, HC9, S =7 Hz), 4.29 and4.39 (AB part of ABX, H₂ C15, J_(A) =11.7 Hz, J=8.1 Hz, J=7.0 Hz), 4.72(dd≈t, HC14, J=8.1 Hz, J=7.0 Hz), 5.23 (dd, HC8, J=15.9 Hz, J=8.0 Hz),5.78 (dd, HC10, J=13.8 Hz J=7.0 Hz), 5.82 (bd, HC7, J=16 Hz), 6.13 (AB,HC12, ,J_(AB) =10.9 Hz), 6.20 (ddAB, HC11, J_(AB) =10.9 Hz, J=13.8 Hz,J=1.0 Hz).

EXAMPLE 2 Removal of HBr from Mixtures of 3a, 3b and 5 with 1, DBN orDBU

A mixture of 3a, 3b and 5 obtained from Example 1 was dissolved inbenzene or toluene (1 mmol in 1 ml) and refluxed with 1.2 equivalents of1, DBN or DBU. The reaction mixture was diluted with ether and washedwith brine until neutral. The crude products were then filtered throughdeactivated alumina (12 g for 5 mmol) to give mixtures of isomers 6a and6b (major) and isomers 7a and 7b (minor). ##STR12##

The following data were obtained from NMR spectroscopy of the resultingproduct:

6a: ¹ H NMR: δ 1.00 (s, H₃ C16,17), 1.42-1.47 (m, H₂ C2), 1.53-1.63 (m,H₂ C3), 1.71 (d, H₃ C18, J=0.7 Hz), 1.90 (d, H₃ C20, J=0.9 Hz), 1.94(bs, H₃ C19), 2.01 (bt, H₂ C4, J=6.2 Hz), 2.03 (s, CH₃ CO), 4.71 (d, H₂C15, J=7.2 Hz), 5.45 (bt, H₂ C14, J=7.2 Hz), 6.02 (d, HC10, J=11.3 Hz),6.18 (d, HC7, J=15.9 Hz), 6.51 (d, HC12, J=15.0 Hz), 6.59 (d, HCS,J=15.9 Hz), 6.76 (dd, HC11a, J=15.0 Hz, J=11.3 Hz); ¹³ C NMR: δ 19.18(C3), 20.36 (H₃ C20), 20.65 (H₃ C19), 20.81 (CH₃ CO), 21.72 (H₃ C18),28.88 (H₃ C16,17), 32.92 (C4), 34.09 (C1), 39.42 (C2), 60.12 (C15),122.51 (C14), 126.49 (C11), 127.17 (C12), 128.61 (C10), 128.85 (C7),129.42 (C5), 129.69 (C8), 135.86 (C9), 137.91-138.03 (C6, C13), 170.73(CO).

6b: ¹ H NMR: a 0.99 (s, H₃ C16,17), 1.42-1.47 (m, H₂ C2), 1.53-1.63 (m,H₂ C3), 1.68 (d, H₃ C18, J=0.6 Hz), 1.92 (d, H₃ C20, J=1.0 Hz), 1.93 (d,H₃ C19, J=0.7 Hz), 1.99 (bt, H₂ C4, J=6.2 Hz), 2.03 (s, CH₃ CO), 4.71(bd, H₂ C15, J=7.2 Hz), 5.45 (t, H₂ C14, J=7.2 Hz), 6.09 (d, HC8, J=16.1Hz), 6.11 (d, HC10, J=11.1 Hz), 6.17 (d, HC7, J=16.1 Hz), 6.57 (d, HC12,J=15.0 Hz), 6.67 (dd, HC11, J=15.0 Hz, J=11.1 Hz); ¹³ C NMR: δ 12.64 (H₃C19), 19.18 (C3), 20.32 (H₃ C20), 20.81 (CH₃ CO), 21.62 (H₃ C18), 28.85(H₃ C16,17), 32.92 (C4), 34.13 (C1), 39.51 (C2), 60.12 (C15), 122.60(C14), 127.22 (C7), 127.62 (C₁₀, 127.88 (C12), 129.30 (C5), 130.08(C10), 137.13 (C9), 137.45 (C8), 137.64 (C13), 137.91-138.033 (C6),170.69 (CO).

EXAMPLE 3 Removal of HBr from Mixtures of 6a, 6b and 7 with Acetonitrileand 1, DBN or DBU

A mixture of 38, 3b and 5 obtained from Example 1 was dissolved inacetonitrile (1 mmol in 1 ml) and stirred at room temperature with 1.2equivalents of 1, DBN or DBU. The reaction mixture was diluted withether and washed with brine until neutral. The crude products were thenfiltered through deactivated alumina (12 g for 5 mmol) to give mixturesof isomers 68 and 6b (major) and isomers 78 and 7b (minor). The NMRspectroscopy data of the resulting products 6a and 6b (major) and thepeaks seen for 78 and 7b (minor) were the same as for Example 2 above.The yields and stereochemical results of HBr elimination from thebromides 3 and 5 are given in Table 1 below.

                                      TABLE I                                     __________________________________________________________________________    Yields and Stereochemical Results of HBr Elimination                          from the Bromides 3 and 5                                                     Starting materials   time,                                                                            Products                                              3a:3b.sup.a                                                                       5:(3a + 3b).sup.b                                                                   Reagent                                                                           Solvent                                                                              min                                                                              6a:6b.sup.c                                                                        7:6.sup.d                                                                        Yield %                                       __________________________________________________________________________    75:25                                                                              9:91 DBN Benzene                                                                              15 66:34                                                                              15:85                                                                            --.sup.e                                      40:60                                                                             30:70 DBN Benzene                                                                              15 40:60                                                                              20:80                                                                            --.sup.e                                      31:69                                                                             23:77 DBN Benzene                                                                              30 36:64                                                                              34:66                                                                            61.sup.f                                      38:62                                                                             10:90 DBN Toluene                                                                              15 42:58                                                                              23:77                                                                            50.sup.f                                      31:69                                                                             23:77 DBN Acetonitrile                                                                         60 36:64                                                                              24:76                                                                            61.sup.f                                      31:60                                                                             23:77 DBU Acetonitrile                                                                         60 37:63                                                                              30:70                                                                            63.sup.f                                      35:65                                                                             20:80 1   Acetonitrile                                                                         60 37:63                                                                              18:82                                                                            49.sup.f                                      31:69                                                                             23:77 1   Acetonitrile                                                                         60 36:64                                                                              22:78                                                                            52.sup.f                                      __________________________________________________________________________     .sup.a Based on relative intensities of H12 signals.                          .sup.b Based on integrals of H9 signals.                                      .sup.c Based on integrals of H.sub.3 C18 signals.                             .sup.d Based on integrals of H14 signals.                                     .sup.e Reaction proceeded to more than 95% completion.                        .sup.f For isolated and purified products. For 1 there was substantially      instantaneous and complete conversion.                                   

P(CH₃ NCH₂ CH₂)₃ N (1) was not effective removing hydrogen bromide fromVitamin A intermediates when the reaction was carded out in refluxingbenzene. Data not shown.

The reaction of a prophosphatrane and acetonitrile with Vitamin Aprecursors 3 and 5 is depicted in Scheme III below: ##STR13##

Dehydrobromination conversion rates were lower using 1 compared with DBNor DBU in refluxing benzene. This observation can be rationalized basedon the greater steric bulk around the basic phosphorus center in 1compared with DBN and DBU. This is especially true as positive charge isbuilt up on 1 when it becomes protonated and transannulated to thetrigonal bipyramidal cation 8.

The superiority of 1 in elfcoting HBr elimination from 3 and 5 inacetonitrile at room temperature over 1 in refluxing benzene resultsfrom the formation of CH₂ CN⁻ which then acts as a sterically small butpowerful base. This conclusion is supported by alp NMR data of theelimination of hydrogen bromide from 3 and 5 with 1 in acetonitrile-d₃.Before addition of the bromides, the ³¹ P NMR spectrum of anacetonitrile-d₃ solution of 1 showed signals of 1 (singlet at 120.8 ppm)and of minute quantities of its deuteriated cation (three lines of equalintensity at -10.0 ppm). When the reaction was complete, a small excessof 1 was still present, while more than 80% of 1 was converted to itsdeuteriated form and less than 20% was found as the protonated species.

The complete disclosures of all patents, patent applications, andpublications are incorporated herein by reference as if each wereindividually incorporated by reference. The invention has been describedwith reference to various specific and preferred embodiments andtechniques. However, it should be understood that many variations andmodifications may be made while remaining within the spirit and scope ofthe invention.

What is claimed is:
 1. A method for deprotonating a compound comprisingtreating the compound with a proazaphosphatrane base in the presence ofa nitrile solvent.
 2. The method of claim 1 wherein theproazaphosphatrane base has the formula: ##STR14## wherein R¹, R² and R³are each individually H, (C₁ -C₁₅)alkyl, (C₆ -C₉)aryl, (C₁ -C₄)alkyl(C₆-C₉)aryl, ((C₁ -C₄)alkyl)₃ Si, or (C₆ -C₉)aryl(C₁ -C₄)alkyl.
 3. Themethod of claim 2 wherein R¹, R² and R³ are each individually H, (C₁-C₈)alkyl, (C₆ -C₉)aryl, or (alk)₃ Si wherein each alk is (C₁ -C₄)alkyl.4. The method of claim 3 wherein R¹, R² and R³ are each individuallyhydrogen or (C₁ -C₈)alkyl.
 5. The method of claim 4 wherein R¹, R² andR³ are each individually hydrogen or (C₁ -C₄)alkyl.
 6. The method ofclaim 5 wherein R¹, R² and R³ are each individually hydrogen or methyl.7. The method of claim 1 wherein the compound is a Vitamin A precursor.8. The method of claim 7 wherein the compound is selected from the groupconsisting of (2Z,4E,8E)-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,8-nonatrien-1-ylacetate and(3E,5E,8E)-2-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohen-1-yl)-3,5,8-nonatrien-1-ylacetate.
 9. The method of claim 1 wherein the nitrile solvent is of theformula R⁴ R⁵ CHCN, wherein R⁴ and R⁵ are each individually hydrogen;saturated or unsaturated, substituted or unsubstituted linear (C₁-C₈)alkyl; or substituted or unsubstituted (C₆ -C₁₄)aryl.
 10. The methodof claim 9 wherein R⁴ and R⁵ are each hydrogen.
 11. The method of claim10 wherein the nitrile solvent is acetonitrile of the formula CH₃ CN.12. The method of claim 1 wherein the deprotonation is carried out atroom temperature.